NAP3在结核病诊断中的价值

目的：研究肺结核患者外周血单个核细胞(PBMCs)经结核特异性抗原刺激后中性粒细胞激活蛋白3(NAP3)的表达情况并与结核潜伏感染(latent tuberculosis infection,LTBI)者及非结核感染健康对照者进行比较。方法提取6例活动期肺结核患者和6例 LTBI 个体 PBMCs,用结核分枝杆菌特异性抗原肽刺激后收集细胞,采用基因芯片分析方法比较两组 NAP3表达情况。然后提取60例活动期肺结核患者和60名 PPD 阳性健康个体(根据γ干扰素表达情况将其分成 LTBI 组和非结核感染健康对照组)的 PBMCs,用结核分枝杆菌特异性抗原肽刺激后,采用酶联免疫吸附试验(ELISA)定量检测刺激前、后细胞培养液上清中 NAP3的浓度。结果基因芯片分析发现活动期肺结核患者 NAP3表达明显高于 LTBI 组(U =1.000,P =0.0043)。ELISA 分析结果发现特异性抗原刺激前细胞培养液上清中3组的 NAP3浓度差异无统计学意义(F =0.7341,P =0.4821),而刺激后只有活动期肺结核组和非结核感染健康对照组之间的 NAP3浓度相比差异有统计学意义(P =0.002)。结论高表达的 NAP3可作为诊断结核的指标之一,但是无法区分潜伏感染和活动期感染病例。     

活动性肺结核患者PBMCs中INHBA基因的表达

目的研究活动性肺结核患者外周血单个核细胞(peripheral blood mononuclear cells, PBMCs)中抑制素βA亚基(inhibin, beta A, INHBA)基因的表达特点。方法使用密度梯度离心法分离PBMCs,然后用TRIzol提取细胞RNA,逆转成cDNA后,进行荧光定量PCR分析INHBA的表达。结果结核分枝杆菌H37Rv菌体裂解液和结核分枝杆菌特异性抗原ESAT-6和CFP-10的多肽,显著性提高PBMCs中INHBA基因的表达,配对t检验p值分别为0.019和0.0013;在无抗原刺激的情况下,活动性肺结核与正常对照之间无显著差别(P=0.52);当使用结核分枝杆菌H37Rv菌体裂解液和结核分枝杆菌特异性抗原ESAT-6和CFP-10的多肽刺激PBMCs,INHBA在活动性肺结核患者组的表达显著性的高于正常对照组,t检验P值分别为0.016和0.010。结论 INHBA在结核抗原刺激后在PBMCs表达显著性升高,且在活动性肺结核患者组显著高于正常对照组,可能作为活动性肺结核的诊断标志物。     

MCP-1在结核病诊断中的价值

目的通过测定外周血单个核细胞(PBMCs)中单核细胞趋化蛋白(MCP-1)的表达水平,探讨其对结核诊断的意义。方法收集活动性肺结核患者、结核潜伏感染(latent tuberculosis infection,LTBI)及非结核感染健康对照个体的全血并提取PBMCs,经结核特异性抗原肽刺激后,采用基因芯片分析方法和酶联免疫吸附试验(ELISA)比较各组MCP-1表达情况。结果基因芯片分析发现活动期肺结核患者MCP-1表达(4460±3154)明显高于LTBI组(951.8±641.5,P=0.0043)。ELISA分析结果发现刺激前三组MCP-1浓度无差异(P=0.4747),而刺激后只有活动期肺结核患者组(37112±3790 pg/ml)和非结核感染健康对照组(15546±3143 pg/ml)之间的MCP-1浓度相比有显著差异(P0.0001)。结论高表达的MCP-1有可能作为诊断结核及监测结核严重程度的指标之一,但是无法区分潜伏感染和活动期感染病例。     

潜伏结核感染相关蛋白抗原的研究进展

结核病是由结核分枝杆菌(Mtb)所致的以呼吸系统感染为主的慢性传染病,潜伏结核感染(LTBI)高危者是结核病预防的关键人群,针对LTBI的早期诊断和高危人群的预防性治疗能有效减少活动性结核病(ATB)发病率。但现有的诊断方法诊断LTBI的特异度较低,因此建立快速、敏感、高效的LTBI诊断方法仍是目前结核病控制工作中面临的重要难题。本文就LTBI相关蛋白抗原的研究进展进行综述,以为LTBI的诊断提供参考。     

血清嗜酸性粒细胞趋化因子、人β-防御素-1对活动性肺结核的鉴别诊断价值及与临床疗效的关系研究

目的 探讨血清嗜酸性粒细胞趋化因子(Eot)、人β-防御素-1(hBD-1)对活动性肺结核(ATB)的鉴别诊断价值,并分析二者与临床疗效的关系。方法 选取2020年3月至2022年10月攀枝花市中心医院收治的162例ATB患者(ATB组),另选取同期81名体检健康者(健康组)及81例潜伏结核感染(LTBI)者(LTBI组),检测并比较三组血清Eot、hBD-1水平,采用受试者工作特征(ROC)曲线分析其对LTBI与ATB的鉴别诊断价值。ATB组患者均予2HRZE/4HR方案治疗,根据疗效分为有效组与无效组,比较两组血清Eot、hBD-1水平。采用多因素logistic回归分析影响ATB患者疗效的危险因素。采用ROC曲线分析血清Eot、hBD-1对疗效的预测价值。结果 ATB组、LTBI组血清Eot水平高于健康组,hBD-1水平低于健康组,差异均有统计学意义(P<0.05)。ATB组血清Eot水平高于LTBI组,hBD-1水平低于LTBI组,差异均有统计学意义(P<0.05)。ROC曲线分析结果显示,血清Eot、hBD-1水平均具有鉴别诊断LTBI与ATB的价值(P<0...     

结核潜伏感染诊断新型候选标志物的筛选及临床验证

目的 筛选及临床验证结核潜伏感染(LTBI)新型候选标志物,为研究LTBI诊断新方法提供科学基础。方法 选择2013年1月至2015年12月就诊于遵义医学院附属医院的活动性肺结核患者(ATB组)、LTBI者(LTBI组)及健康人群(H组)血清。小样本分别独立地与包含4262个结核分枝杆菌(MTB)重组蛋白的Mtbprot^TM芯片反应进行初筛,选择差异较为明显的蛋白质,定制成蛋白小芯片,进行较大样本验证,对有效数据进行归一化处理,根据单个蛋白的P值进行评价,进一步通过SPSS统计软件,优化出最优组合。结果 用Mtbprot^TM芯片,经32份血清(H组7份、LTBI组9份及ATB组16份)试验验证,初筛出前100个可能与LTBI相关蛋白质,用这些蛋白质制成小芯片,分别与204份血清(H组44份,LTBI组60份,ATB组100份)进行进一步验证试验,优选出8个蛋白标志物,分别为Rv1860、Rv2031c、Rv1441c、Rv0494、Rv3301c、Rv0351、Rv1821和Rv0280,其组合诊断LTBI的特异性及敏感性分别为90.9%和83.1%。结论 成功筛选鉴定出8个LTBI新型候选蛋白标志物,其组合应用在LTBI诊断和鉴别诊断上具有较大的潜在应用前景。     

miRNA-192调控NOD2在结核分枝杆菌感染中的作用研究

目的探讨miRNA-192调控NOD2在结核分枝杆菌感染中的作用。方法收集2018年1月-2018年12月新疆医科大学第一附属医院确诊为活动性肺结核患者和非结核健康对照者的外周血标本,其中活动性肺结核组93例,健康对照组83例,采用miRanda软件预测NOD2 3'UTR与miRNA-192是否有结合位点;通过qRT-PCR检测miRNA-192和NOD2 mRNA的相对表达量;通过ELISA检测相关细胞因子IL-6、TNF-α、IFN-γ在血清中的表达情况。结果 miRanda软件预测NOD2 3'UTR中存在miRNA-192的结合位点;qRT-PCR检测miRNA-192和NOD2 mRNA在两组受检者的外周血白细胞中均有表达,其中miRNA-192在活动性肺结核组的表达(5.07±5.66)较健康对照组(0.43±1.13)增加,NOD2 mRNA在活动性肺结核组的表达(1.91±0.12)较健康对照组(1.00±0.63)也增加;ROC曲线分析显示,miRNA-192和NOD2 mRNA肺结核诊断的ROC曲线下面积分别为0.8458(95%CI为0.7997-0.9485)、0.7674(95%CI为0.6674-0.8615),特异性为89.55%和77.94%,敏感度为68.12%和68.06%;活动性肺结核组患者血清IFN-γ、IL-6和TNF-α分别为(36.39±9.24)pg/ml、(62.39±15.37)pg/ml和(77.99±18.82)pg/ml,健康对照组分别为(15.99±4.88)pg/ml、(31.68±7.85)pg/ml和(64.22±20.90)pg/ml,差异均具有统计学意义(P0.01)。结论结核分枝杆菌感染机体时,高表达的miRNA-192使NOD2 mRNA表达增强,促进相关炎性因子高表达,这对肺结核的发生发展及防治具有临床意义。     

基于组学检测的结核病发病风险研究进展

结核病严重威胁着人类健康,防控形势严峻,研究其发病风险的检测有助于结核病的防治。我国结核感染人数众多,绝大多数患者为潜伏结核感染(Latent Tuberculosis Infection,LTBI),是内源性发病的库源,5%~10%的潜伏感染者会在一生中发生结核病。对LTBI患者进行风险性预测和干预治疗,防止其发展为活动性结核病在结核病防治中具有重要作用。目前尚无诊断LTBI的金标准,也没有权威发布用于预测感染后发病风险的生物学预警指标。本文从转录组学、蛋白组学和免疫组学3方面对LTBI进展到活性结核病的研究进展进行综述,并对结核病发病风险的检测研究方向进行了展望。     

检测外周血特异性结核分枝杆菌抗体对活动性结核病的诊断价值研究

目的研究外周血浆细胞分泌特异性结核分枝杆菌抗体对活动性结核病的诊断价值。方法纳入2013年4月至7月期间深圳市第三人民医院肺科门诊活动性结核病患者;健康对照组人员来自体检科门诊志愿者,分为3个组：活动性结核病组（104例）、结核分枝杆菌（Mtb）潜伏感染组（26例）和健康对照组（33名）。分离其外周血单个核细胞（PBMCs）。体外培养4d后收集培养上清液,用ELISA法和蛋白免疫印迹法,ELISA和蛋白免疫印迹法检测外周血浆细胞分泌的特异性结核分枝杆菌抗体;检测各组收集的PBMCs培养上清液中的特异性结核分枝杆菌抗体,比较各组间的差异。所有数据均使用GraphPadPrism5．0进行统计学分析,用受试者工作特征（ROC）曲线评价ELISA法检测的诊断价值,得出敏感度、特异度;多组间的比较采用Kruskal—Wallis检验;两组间比较采用Dunnmultiplecomparison检验;蛋白免疫印迹法用四格表的卡方检验;以P〈0．05为差异有统计学意义。结果ELISA法检测活动性结核病组特异性结核分枝杆菌抗体的A450nm值（0．593±0．206）高于Mtb潜伏感染组（0．342±0．152）和健康对照组（0．246±0．121）,差异有统计学意义（H=77．27,P〈0．001）。特异性结核分枝杆菌抗体区分活动性结核病患者和Mtb潜伏感染者、健康对照者曲线下面积（AUC）分别为0．857、0．944,当诊断界限值为0．42时,其区分活动性结核病和Mtb潜伏感染的敏感度为77．9％（81／104）,特异度为80．8％（21／26）;区分活动性结核病和健康人的敏感度为77．9％（81／104）,特异度为93．9％（31／33）。蛋白免疫印迹法检测活动性结核病和健康人的敏感度、特异度和准确性分别为79．2％（61／77）、100．0％（11／11）、81．8％（72／88）（x2=24．8,P〈0．001）。结论ELISA法和蛋白免疫印迹法检测外周血浆细胞分泌特异性结核分枝杆菌抗体诊断活动性结核病特异度高,可以作为临床结核病实验诊断的辅助方法。     

结核分枝杆菌潜伏感染的治疗:利大于弊还是弊大于利

结核病仍然是全球十大死因之一。结核分枝杆菌潜伏感染(LTBI)是指结核分枝杆菌感染人体后,未发生活动性结核病,但具有发展为活动性结核病的风险。文章针对LTBI治疗充分阐述利弊,并结合中国结核病现实状况,提出在中国需要进行逐步的完善相关人群的预防治疗,逐渐由点到面推广LTBI的治疗,把结核病消灭在LTBI状态,降低结核病发病率,达到世界卫生组织提出的2035年消灭结核病的目标。     

胰岛素瘤的解剖分布特点分析

目的胰岛素瘤是最常见的胰腺神经内分泌肿瘤，因其临床表现多样，导致诊断困难。影像学诊断尤其是超声内镜(EUS)在胰岛素瘤的诊断中起着重要作用，拥有较高的敏感性和特异性。本研究拟通过明确胰岛素瘤的解剖分布特点，以期有助于提高影像学的诊断准确率和降低漏诊率，尤其是在教育和培训实践中对于EUS的学习者更具有指导价值。 方法回顾性分析解放军总医院第一医学中心病案资料数据库1993年1月至2019年11月经外科手术、病理确诊为胰岛素瘤的患者的临床资料，检索方法采取搜索术后病理诊断为"胰岛素瘤"的病例，通过查阅病例的方法，提取出胰岛素瘤的大小和解剖分布等数据，进一步分析其特点。 结果共检索到确诊为胰岛素瘤的患者116例，其中，男45例、女71例，年龄13～76岁，平均年龄(44.4±14.85)岁。胰岛素瘤单发110例(94.8%)、多发6例(5.2%)。位置分布：头颈部46例(39.7%)，单发45例、多发1例；体尾部68例(58.6%)，单发65例、多发3例；全胰腺多发2例(1.7%)。病变大小特点：最大径0.4～3.4 cm，平均大小(1.53±0.58)cm。≤1 cm 29例、>1 cm而≤1.5 cm41例、>1.5 cm而≤2.0 cm28例，≤3 cm 15例，>3 cm 3例。年龄与肿瘤的大小相关，≤44岁患者肿瘤平均大小为(1.36±0.51)cm、>44岁患者肿瘤平均大小为(1.70±0.60)cm，P<0.05。头颈部的肿瘤大于体尾部的肿瘤，头颈部肿瘤平均大小(1.66±0.63)cm，体尾部(1.42±0.52)cm，P<0.05。 结论胰岛素瘤在胰腺体尾部较头颈部更好发；绝大多数单发，但可以全胰腺多发；多数小于1.5 cm，肿瘤的大小与患者年龄和肿瘤的解剖分布相关。     

Pathogenesis of carcinoma of the papilla of Vater

Most adenomas and carcinomas of the small intestine and extrahepatic bile ducts arise in the region of the papilla of Vater. In familial adenomatous polyposis (FAP) it is the main location for carcinomas after proctocolectomy. In many cases symptoms due to stenosis lead to diagnosis at an early tumor stage. In about 80%, curative intended resection is possible. Operability is the most relevant prognostic factor. Most ampullary carcinomas resp. carcinomas of the papilla of Vater develop from adenomatous or flat dysplastic precursor lesions. They can be sited in the ampulloduodenal part of the papilla of Vater, which is lined by intestinal mucosa. They also can develop in deeper parts of the ampulla, which are lined by pancreaticobiliary duct mucosa. Intestinal-type adenocarcinoma and pancreaticobiliary-type adenocarcinoma represent the main histological types of ampullary carcinoma. Furthermore, there exist unusual types and undifferentiated carcinomas. Many carcinomas of intestinal type express the immunohistochemical marker profile of intestinal mucosa (keratin 7?, keratin 20+, MUC2+). Carcinomas of pancreaticobiliary type usually show the immunohistochemical profile of pancreaticobiliary duct mucosa (keratin 7+, keratin 20?, MUC2?). Even poorly differentiated carcinomas, as well as unusual histological types, may conserve the marker profile of the mucosa they developed from. These findings underline the concept of histogenetically different carcinomas of the papilla of Vater which develop either from intestinal- or from pancreaticobiliary-type mucosa of the papilla of Vater. Molecular alterations in ampullary carcinomas are similar to those of colorectal as well as pancreatic carcinomas, although they appear at different frequencies. In future studies, molecular alterations in ampullary carcinomas should be correlated closely with the different histologic tumor types. Consequently, the histologic classification should reflect the histogenesis of ampullary tumors from the two different types of papillary mucosa.     

Lack of correlation of degree of villous atrophy with severity of clinical presentation of coeliac disease

BACKGROUND AND AIM: Both the clinical presentation and the degree of mucosal damage in coeliac disease vary greatly. In view of conflicting information as to whether the mode of presentation correlates with the degree of villous atrophy, we reviewed a large cohort of patients with coeliac disease. PATIENTS AND METHODS: We correlated mode of presentation (classical, diarrhoea predominant or atypical/silent) with histology of duodenal biopsies and examined their trends over time. RESULTS: The cohort consisted of 499 adults, mean age 44.1 years, 68% females. The majority had silent coeliac disease (56%) and total villous atrophy (65%). There was no correlation of mode of presentation with the degree of villous atrophy (p=0.25). Sixty-eight percent of females and 58% of males had a severe villous atrophy (p=0.052). There was a significant trend over time for a greater proportion of patients presenting as atypical/silent coeliac disease and having partial villous atrophy, though the majority still had total villous atrophy. CONCLUSIONS: Among our patients the degree of villous atrophy in duodenal biopsies did not correlate with the mode of presentation, indicating that factors other than the degree of villous atrophy must account for diarrhoea in coeliac disease.     

Demonstration of the mechanism of action of biguanides

Summary Palmitic acid oxidation in rat diaphragm homogenate is depressed by biguanide concentrations that are still incapable of inhibiting oxidative phosphorylation. Glucose oxidation is not directly effected by the same biguanide concentrations: however, the inhibitory effect of palmitic acid on glucose oxidation is partly removed by biguanides. Inhibition of fatty acid oxidation, which accounts for most of the metabolic effects caused by these drugs, can be regarded as the fundamental mechanism of action of biguanides. There is some evidence suggesting that these drugs might interact with carnitine, thus preventing long-chain fatty acids from being transported across the mitochondrial membrane to the site of oxidation. Traduzione a cura degli AA.     

血吸虫童虫生长发育及其机制的研究进展

血吸虫童虫是宿主免疫系统攻击的重要靶标,包括皮肤型、肺型和肝门型童虫。宿主分子对童虫生长发育具有重要作用。童虫生长发育机制包括免疫调节、信号转导、性别发育及凋亡等。肌动蛋白、组织蛋白酶、烯醇化酶和葡萄糖基转移酶等分子为血吸虫童虫生长发育的重要分子。本文对血吸虫童虫生长发育及其机制的研究进展做一综述。     

124例耐多药结核分枝杆菌基因突变特征分析

目的对临床分离的耐多药结核分枝杆菌相关基因的突变特征进行分析。方法对124例耐多药结核分枝杆菌以及50株敏感株的耐药相关基因(包括异烟肼inh A、kat G、oxyR-ahp C间隔区以及利福平rpo B)进行序列测定,分析其基因突变情况。结果异烟肼耐药inh A基因突变率为14.5%;kat G基因突变率为70.2%(87/124),主要位于315位;oxyR-ahp C间隔区突变率为15.3%;inh A、kat G两种基因同时突变率75.0%,三种基因同时突变率为89.5%。利福平rpo B基因突变的检出率高达95.2%,突变主要发生在531、526、516位点。结论我省耐多药菌异烟肼耐药相关基因最常见突变为kat G 315、inh A C-T(-15)、axyR-ahp C间隔区(-10)C-T,利福平为rpo B531、526、516。结合MDR-TB耐药相关基因的特征分析,可以建立一种快速、准确、特异的适合于我省的检测结核菌耐多药性的新方法。     

Assessment of quality of life of parents of children with juvenile chronic arthritis

The aim of the study was to assess the quality of life (QOL) and the psychological status of parents of children with juvenile chronic arthritis (JCA). The QOL, anxiety and depression of the parents of 28 children with JCA were evaluated and compared to those of the parents of 28 healthy children. Mothers of JCA children and mothers of healthy children reported similar QOL. The reported anxiety and depression levels were similar for mothers and fathers in both groups. The parents of children with pauciarticular-type JCA reported lower QOL and higher levels of anxiety and depression than the parents of children with other types, namely polyarticular and systemic JCA. These findings may be explained by the fact that the pauciarticular patients had shorter disease duration and were less frequently seen in the outpatient clinic. The QOL of mothers of children with JCA was found to be slightly impaired in the group of children with pauciarticular JCA. Future larger studies are needed to confirm these results, as the number of subjects in the three groups was rather low. Received: 26 September 2001 / Accepted: 8 February 2002     

氯硝柳胺悬浮剂的毒性评价

目的评价氯硝柳胺悬浮剂的毒性，为现场大规模应用灭螺提供依据。方法按照中华人民共和国国家标准GB 15670-1995《农药登记毒理学试验方法》和鱼类毒性试验方法进行。结果经口、经皮肤的LDso雌、雄性大鼠均>5 000 mg/kg，经呼吸道的LCso雌、雄性大鼠均>5 000mg/m3，该药经口、经皮肤、经呼吸道毒性均属微毒类药物；兔眼用药后，观察期内无不良反应，对眼无刺激性；皮肤用药后对皮肤无刺激性。与氯硝柳胺原药、氯硝柳胺乙醇胺盐原药和氯硝柳胺乙醇胺盐可湿性粉剂相比，氯硝柳胺悬浮剂对鱼急性毒性最低。结论氯硝柳胺悬浮剂属微毒类药物，对鱼的毒性低于其乙醇胺盐可湿性粉剂，适合于现场应用。     

Numerical Simulation of the Effect of Rate of Change of Glucose on Measurement Error of Continuous Glucose Monitors

Background

A 5-day in-patient study designed to assess the accuracy of the FreeStyle Navigator® Continuous Glucose Monitoring System revealed that the level of accuracy of the continuous sensor measurements was dependent on the rate of glucose change. When the absolute rate of change was less than 1 mg•dl⁻¹•min⁻¹ (75% of the time), the median absolute relative difference (ARD) was 8.5%, with 85% of all points falling within the A zone of the Clarke error grid. When the absolute rate of change was greater than 2 mg•dl⁻¹•min⁻¹ (8% of the time), the median ARD was 17.5%, with 59% of all points falling within the Clarke A zone.

Method

Numerical simulations were performed to investigate effects of the rate of change of glucose on sensor measurement error. This approach enabled physiologically relevant distributions of glucose values to be reordered to explore the effect of different glucose rate-of-change distributions on apparent sensor accuracy.

Results

The physiological lag between blood and interstitial fluid glucose levels is sufficient to account for the observed difference in sensor accuracy between periods of stable glucose and periods of rapidly changing glucose.

Conclusions

The role of physiological lag on the apparent decrease in sensor accuracy at high glucose rates of change has implications for clinical study design, regulatory review of continuous glucose sensors, and development of performance standards for this new technology. This work demonstrates the difficulty in comparing accuracy measures between different clinical studies and highlights the need for studies to include both relevant glucose distributions and relevant glucose rate-of-change distributions.     

治疗高血压药物的经济学评价

重视高血压治疗中的经济学评价,对利用我国有限的卫生资源来遏制高血压对人民群众的危害有着重要的现实意义。药物经济学对于药物治疗的成本和治疗的结果给予同样的关注。因为治疗高血压的费用,不仅涉及药物价格,还包括患者的危险水平,降压疗效和对临床终点事件的影响,以及治疗的依从性和安全性。因此药物经济学更强调整体成本和价-效比。低危病人,若非药价低廉,治疗的价-效比不够理想。而在高危的患者,价-效比越小越经济而不是药费越便宜越好。